BIO101 – From Two Cells To Many: Cell Differentiation and Embryonic Development

As you may know, I have been teaching BIO101 (and also the BIO102 Lab) to non-traditional students in an adult education program for about twelve years now. Every now and then I muse about it publicly on the blog (see this, this, this, this, this, this and this for a few short posts about various aspects of it – from the use of videos, to the use of a classroom blog, to the importance of Open Access so students can read primary literature). The quality of students in this program has steadily risen over the years, but I am still highly constrained with time: I have eight 4-hour meetings with the students over eight weeks. In this period I have to teach them all of biology they need for their non-science majors, plus leave enough time for each student to give a presentation (on the science of their favourite plant and animal) and for two exams. Thus I have to strip the lectures to the bare bones, and hope that those bare bones are what non-science majors really need to know: concepts rather than factoids, relationship with the rest of their lives rather than relationship with the other sciences. Thus I follow my lectures with videos and classroom discussions, and their homework consists of finding cool biology videos or articles and posting the links on the classroom blog for all to see. A couple of times I used malaria as a thread that connected all the topics – from cell biology to ecology to physiology to evolution. I think that worked well but it is hard to do. They also write a final paper on some aspect of physiology.

Another new development is that the administration has realized that most of the faculty have been with the school for many years. We are experienced, and apparently we know what we are doing. Thus they recently gave us much more freedom to design our own syllabus instead of following a pre-defined one, as long as the ultimate goals of the class remain the same. I am not exactly sure when am I teaching the BIO101 lectures again (late Fall, Spring?) but I want to start rethinking my class early. I am also worried that, since I am not actively doing research in the lab and thus not following the literature as closely, that some of the things I teach are now out-dated. Not that anyone can possibly keep up with all the advances in all the areas of Biology which is so huge, but at least big updates that affect teaching of introductory courses are stuff I need to know.

I need to catch up and upgrade my lecture notes. And what better way than crowdsource! So, over the new few weeks, I will re-post my old lecture notes (note that they are just intros – discussions and videos etc. follow them in the classroom) and will ask you to fact-check me. If I got something wrong or something is out of date, let me know (but don’t push just your own preferred hypothesis if a question is not yet settled – give me the entire controversy explanation instead). If something is glaringly missing, let me know. If something can be said in a nicer language – edit my sentences. If you are aware of cool images, articles, blog-posts, videos, podcasts, visualizations, animations, games, etc. that can be used to explain these basic concepts, let me know. And at the end, once we do this with all the lectures, let’s discuss the overall syllabus – is there a better way to organize all this material for such a fast-paced class.

Follow me under the fold:It’s Thursday, so it is time for the next portion of my BIO101 lecture notes (May 15, 2006). As alway, I’d appreciate corrections of errors, and suggestions for improvement.
————————————————————————–Cell Differentiation and Embryonic DevelopmentBIO101 – Bora Zivkovic – Lecture 2 – Part 2
There are about 210 types of human cells, e.g., nerve cells, muscle cells, skin cells, blood cells, etc. Wikipedia has a nice comprehensive listing of all the types of human cells.

What makes one cell type different from the other cell types? After all, each cell in the body has exactly the same genome (the entire DNA sequence). How do different cells grow to look so different and to perform such different functions? And how do they get to be that way, out of homogenous (single cell type) early embryonic cells that are produced by cell division of the zygote (the fertilized egg)?

The difference between cell types is in the pattern of gene expression, i.e., which genes are turned on and which genes are turned off. Genes that code for enzymes involved in detoxification are transribed in lver cells, but there is not need for them to be expressed in muscle cells or neurons. Genes that code for proteins that are involved in muscle contraction need not be transcribed in white blood cells. The patterns of gene expression are specific to cell types and are directly resposible for the differences between morphologies and functions of different cells.

How do different cell types decide which genes to turn on or off? This is the result of processes occuring during embryonic development.

The zygote (fertilized egg) appears to be a sphere. It may look homogenous, i.e., with no up and down, left or right. However, this is not so. The point of entry of the sperm cell into the egg may provide polarity for the cell in some organisms. In others, mother may deposit mRNAs or proteins in one particular part of the egg cell. In yet others, the immediate environment of the egg (e.g., the uterine lining, or the surface of the soil) may define polarity of the cell.

When the zygote divides, first into 2, then 4, 8, 16 and more cells, some of those daughter cells are on one pole (e.g., containing maternal chemicals) and the others on the other pole (e.g., not containing maternal chemicals). Presence of chemicals (or other influences) starts altering the decisions as to which genes will be turned on or off.

As some of the genes in some of the cells turn on, they may code for proteins that slowly diffuse through the developing early embryo. Low, medium and high concentrations of those chemicals are found in diferent areas of the embryo depending on the distance from the cell that produces that chemical.

Other cells respond to the concentration of that chemical by turning particular genes on or off (in a manner similar to the effects of steroid hormones acting via nuclear receptors, described last week). Thus the position (location) of a cell in the early embryo largely determines what cell type it will become in the end of the process of the embryonic development.

The process of altering the pattern of gene expression and thus becoming a cell of a particular type is called cell differentiation.

The zygote is a totipotent cell – its daughter cells can become any cell type. As the development proceeds, some of the cells become pluripotent – they can become many, but not all cell types. Later on, the specificity narrows down further and a particular stem cell can turn into only a very limited number of cell types, e.g., a few types of blood cells, but not bone or brain cells or anything else. That is why embryonic stem cell research is much more promising than the adult stem cell research.

The mechanism by which diffusible chemicals synthesized by one embryonic cell induces differentiation of other cells in the embryo is called induction. Turning genes on and off allows the cells to produce proteins that are neccessary for the changes in the way those cells look and function. For instance, development of the retina induces the development of the lens and cornea of the eye. The substance secreted by the developing retina can only diffuse a short distance and affect the neighboring cells, which become other parts of the eye.

During embryonic development, some cells migrate. For instance, cells of the neural crest migrate throughout the embryo and, depending on their new “neighborhood” differentiate into pigment cells, cells of the adrenal medula, etc.

Finally, many aspects of the embryo are shaped by programmed cell death – apoptosis. For instance, early on in development our hands look like paddles or flippers. But, the cells of our fingers induce the cell death of the cells between the fingers. Similarly, we initially develop more brain cells than we need. Those brain cells that establish connections with other nerve cells, muscles, or glands, survive. Other brain cells die.

Sometimes just parts of cells die off. For instance, many more synapses are formed than needed between neurons and other neurons, muscles and glands. Those synapses that are used remain and get stronger, the other synapses detach, and the axons shrivel and die. Which brain cells and which of their synapses survive depends on their activity. Those that are involved in correct processing of sensory information or in coordinated motor activity are retained. Thus, both sensory and motor aspects of the nervous system need to be practiced and tested early on. That is why embryos move, for instance – testing their motor coordination. That is why sensory deprivation in the early childhood is detrimental to the proper development of the child.

The details of embryonic development and mechanisms of cell differentiation differ between plants, fungi, protists, and various invertebrate and vertebrate animals. We will look at some examples of those, as well as some important developmental genes (e.g., homeotic genes) in future handouts/discussions, and will revisit the human development later in the course.